Mechanisms involved in the central nervous system effect of three endogenous peptides, thyrotropin-releasing hormone (TRH), luteinizing hormone-releasing hormone (LHRH) and neurotensin (NT) have been investigated. Electrolytic lesion studies have revealed that: (1) destruction of the organum vasculosum of the lamina terminalis (OVLT) does not abolish LHRH-induced lordosis behavior in estrogen-primed ovariectomized female rats; (2) destruction of brain regions rich in endogenous NT, inducing the n.accumbens, preoptic area, dorsomedial thalamus and interpeduncular nuclei does not abolish NT-induced hypothermia in rats. Intracerebroventricular (ICV) NT in MSG-treated rats produced a significant hypothermia, indicating that the brain areas damaged by neonatal MSG treatment are not essential for NT-induced hypothermia. Direct injection of NT into the preoptic area or the n.accumbens did not produce hypothermic response. Receptor studies have revealed that TRH and NT do not alter the in vitro binding of 3H-spiroperidol to membranes (dopamine receptors) derived from n.accumbens or striatum. Binding of 3H-naloxone to opiate receptors is also unaffected by TRH and NT. Pharmacological blockade of opiate receptors (naltrexone), or muscarinic cholinergic receptors (atropine), alpha adrenergic (phenoxybenzamine), and beta-adrenergic (propranolol) receptors did not alter NT-induced hypothermia in rats. However, intracisternal (IC) injection of TRH partially but significantly antagonized NT-induced hypothermia. Although depletion of brain serotonin with parachlorophenylalanine (pepa) did not block NT-induced hypothermia, 6-hydroxydopamine (60HDA) (depletion of brain DA and norepinephrine, NE) treated animals exhibited a significantly augmented hypothermic response after IC NT. Further study revealed that haloperidol also potentiates NT-induced hypothermia. These data suggest interactions of NT with brain DA systems.